Bipolar Androgen Therapy + Carboplatin in mCRPC

NCT03522064 | Recruiting Phase 2 DMC

• 1 other identifier: HiTECH
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy of BAT and carboplatin in men with metastatic castrate-resistant prostate cancer (mCRPC).

Conditions

Homologous Recombination Deficiency; Castration-resistant Prostate Cancer

Keywords

Castrate-resistant prostate cancer; bipolar androgen therapy; homologous recombination deficiency; BRCA

Outcome Measures

Primary Outcomes (1)

• PSA Response Rate

  \>/= 50% fall from baseline PSA

  1 year

Secondary Outcomes (3)

• Time to PSA progression

  1 year

• Radiological Response Rate

  1 year

• Safety and Tolerability (Frequency of adverse events as assessed by NCI CTCAE v4.0)

  1 year

Other Outcomes (2)

• Changes in ctDNA expression from baseline

  1 year

• Change in serum testosterone and oestradiol levels

  1 year

Study Arms (1)

High dose testosterone + Carbolplatin

EXPERIMENTAL

500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy) plus Carboplatin AUC 5

Drug: Testosterone Enanthate 100 MG/ML Injectable Solution; Drug: Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5

Interventions

Testosterone Enanthate 100 MG/ML Injectable Solution DRUG

Testosterone Enanthate is the oil-soluble ester of the androgenic hormone testosterone. Testosterone Enanthate is a clear to pale yellow solution for intramuscular injection. Each pre-filled syringe contains 250mg testosterone enanthate/1mL.

Also known as: Primoteston Depot

High dose testosterone + Carbolplatin

Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5 DRUG

Testosterone Enanthate is the oil-soluble ester of the androgenic hormone testosterone. Testosterone Enanthate is a clear to pale yellow solution for intramuscular injection. Each pre-filled syringe contains 250mg testosterone enanthate/1mL. Carboplatin as per standard procedures

High dose testosterone + Carbolplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males with histologically confirmed adenocarcinoma of the prostate
• Confirmed HRD (Homologous recombination defect) in germline and/or somatic DNA analysis (tumour or blood), by a validated assay (see Appendix 1). Mutations in HR genes not listed in appendix 1 will be considered in literature suggests pathogenicity. A maximum of 10 uncharacterised or heterozygous mutations will be included.
• Age ≥ 18 years
• ECOG performance status ≤ 1
• Rising PSA confirmed on two sequential tests ≥1 week apart and a minimum value of 2 ug/L despite castrate levels of testosterone
• Serum testosterone \< 1.7 nmol/L and on an LHRH agent or post orchidectomy ≥ 1 year.
• Washout of ≥ 4 weeks from prior line of treatment, radiotherapy or surgery (aside from LHRH agent)
• Adequate bone marrow function (platelets \> 100 x 109/L, ANC \> 1.5 x 109/L, Hb \>100)
• Adequate liver function (ALT/AST \< 1.5 x ULN, bilirubin \< 2 x ULN)
• Adequate renal function (creatinine clearance \> 50 ml/min)
• Adequate cardiac function and reserve after cardiology assessment
• Archived tissue sample available or willingness to undergo fresh biopsy
• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
• Signed, written informed consent

You may not qualify if:

• Contraindications to investigational product
• Pain due to metastatic prostate cancer requiring opioid analgesics
• Evidence of disease progression in sites or extent that, in the opinion of the investigator, would put the patient at risk from testosterone therapy and its potential for initial tumour flare (eg: femoral metastasis at risk of fracture, ureteric obstruction due to nodal disease or cord compression due to spinal metastases).
• Previous treatment with platinum chemotherapy and/or a PARP inhibitor. However up to 8 men with prior treatment to these agents will be included as an exploratory cohort.
• Life expectancy of less than 3 months.
• Brain metastases or leptomeningeal disease
• History of thromboembolic event and not currently on anticoagulation
• Prior myocardial infarction or unstable angina within 2 years of study entry
• Haematocrit ≥ 50%, untreated severe obstructive sleep apnoea or poorly controlled heart failure (NYHA \>1)
• History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment.
• Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead

Study Sites (1)

Kinghorn Cancer Centre, St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

RECRUITING

Related Publications (3)

• Teply BA, Wang H, Luber B, Sullivan R, Rifkind I, Bruns A, Spitz A, DeCarli M, Sinibaldi V, Pratz CF, Lu C, Silberstein JL, Luo J, Schweizer MT, Drake CG, Carducci MA, Paller CJ, Antonarakis ES, Eisenberger MA, Denmeade SR. Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study. Lancet Oncol. 2018 Jan;19(1):76-86. doi: 10.1016/S1470-2045(17)30906-3. Epub 2017 Dec 14.

  PMID: 29248236 BACKGROUND

• Schweizer MT, Wang H, Luber B, Nadal R, Spitz A, Rosen DM, Cao H, Antonarakis ES, Eisenberger MA, Carducci MA, Paller C, Denmeade SR. Bipolar Androgen Therapy for Men With Androgen Ablation Naive Prostate Cancer: Results From the Phase II BATMAN Study. Prostate. 2016 Sep;76(13):1218-26. doi: 10.1002/pros.23209. Epub 2016 Jun 24.

  PMID: 27338150 BACKGROUND

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

  PMID: 32203306 DERIVED

MeSH Terms

Interventions

testosterone enanthate

Study Officials

• Anthony M Joshua, MBBS, PhD, FRACP

  St Vincent's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Kent

CONTACT

+61293555611; SVHS.CancerResearch@svha.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 11, 2018
• Study Start: July 30, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 23, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)